Dr Holger Gerhardt, Max Delbrueck Centre for Molecular Medicine (MDC)
Professor Yaakov Nahmias, Hebrew University of Jerusalem
Stem cells have a unique capacity to proliferate and differentiate, promising an unlimited supply of cells for regenerative medicine. Stem cell derived hepatocytes can be used to treat liver failure or genetic deficiencies. In fact, liver failure accounts for over 25,000 deaths a year in the United States, but less than 7,000 livers are available for transplantation. Stem cell technologies can enable us to bridge this gap by creating new livers from human cells. However, previous techniques result in cells with low level of metabolic function and limited abilities to survive transplantation. The few cells that do survive transplantation display high level of function suggesting that the environment provides critical cues necessary for maturation Small blood vessels are an important component of the environment, controlling oxygen and nutrient supply, while providing factors needed for the maturation of tissues, such as liver and pancreas. However, studying the role of capillaries in liver development is difficult as there are no methods to build functional capillaries in a dish.
In this project, Dr Gerhardt and Professor Nahmias developed techniques for producing more metabolically functional and mature liver cells, from stem cells, than ever before. They were further able to create micro liver tissue with sprouting of small blood vessels, outside the body, thereby increasing their understanding of the function of the vascular network in promoting liver development and maturation. The researchers also gained a better understanding of the biological response of endothelial cells to blood flow perfusion, thanks to the creation of an original device. Their discoveries provide novel platform to study endothelial cell response to flow, and for the study of liver regeneration, cancer formation, and drug discovery, bringing us one step closer to creating human liver tissues with the potential to replace orthotropic liver transplantations artificially.